Oligodendrocyte Lineage Cell Mechanisms of Axon Selection for Myelination

少突胶质细胞系髓鞘形成轴突选择的细胞机制

• 批准号: 10386033
• 负责人: Natalie J Carey
• 金额: $ 3.8万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-04 至 2024-11-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10386033
• 关键词: Action Potentials; Address; Axon; Cell Adhesion Molecules; Cell Lineage; Cells; Code; Data; Detection; Development; Dominant-Negative Mutation; Electric Capacitance; Fire - disasters; Fluorescent in Situ Hybridization; Gene Expression; Gene Proteins; Genes; Genetic; Glutamates; Health; Imaging Device; Impaired cognition; In Situ Hybridization; Individual; Interneurons; Light; Mediating; Membrane; Metabolic; Modeling; Molecular; Motor; Myelin; Myelin Sheath; Nature; Neuraxis; Neurons; Neurotransmitters; Oligodendroglia; Output; Pattern; Phenotype; Play; Positioning Attribute; Process; Property; Proteins; RNA; Recording of previous events; Reporter; Role; Scaffolding Protein; Selection Bias; Signal Transduction; Specificity; Spinal; Synapses; Synaptic Vesicles; Testing; Time; Transgenic Organisms; Translating; Work; Zebrafish; base; cell type; density; experimental study; genetic approach; gephyrin; imaging study; in vivo; in vivo imaging; insight; loss of function; myelination; neural circuit; neurotransmission; oligodendrocyte lineage; protein function; scaffold; theories; vesicular release

PROJECT SUMMARY Oligodendrocytes are the resident myelinating cell type of the central nervous system. Recent work indicates that different classes of neurons have differing patterns and distribution of myelin along their axons. Yet only recently has the identity of the axons been considered with respect to myelination. Thus, the mechanisms of axon signaling and selection for myelination remain largely unknown. Our lab and others have shown that neuronal activity increases myelination and synaptic vesicle release occurs along axons underneath myelin sheaths, suggesting oligodendrocytes may need to be able to receive and interpret neurotransmitter signaling. A single oligodendrocyte can myelinate up to 40 distinct axons, posing a unique situation where an individual cell may need to adapt to signaling from many different neurons. How might this be achieved? Oligodendrocytes express many canonical post-synaptic factors, ostensibly to aid in signaling between the axon and myelin sheath, but the role these proteins play in myelinating cells is largely unknown. Using a zebrafish model, this proposal will utilize genetic approaches and in vivo imaging to address two fundamental concepts: is there a pattern to the expression and/or localization of these post-synaptic factors in oligodendrocytes and does this correspond to wrapped axonal identity; and what function do they serve in the process of myelination. This will be achieved in two aims: Aim 1 tests what post-synaptic factors are expressed, where these post-synaptic proteins localize, and when are they important; and Aim 2 tests how these proteins function to facilitate myelination, and if there is a correlation between axon identity and localization and function of post-synaptic proteins in myelinating oligodendrocytes.

项目摘要 少突胶质细胞是中枢神经系统的常驻细胞类型。最近的工作表明 不同类别的神经元具有不同的模式和髓磷脂沿轴突的分布。只有 最近，是否考虑了轴突的身份。因此，机制 轴突信号传导和髓鞘化的选择在很大程度上未知。我们的实验室和其他实验室表明 神经元活动增加髓鞘形成和突触囊泡释放，沿髓鞘下方的轴突发生 鞘，表明少突胶质细胞可能需要能够接收和解释神经递质信号传导。 单个少突胶质细胞最多可髓鞘40个不同的轴突，这是一个独特的情况 细胞可能需要适应许多不同神经元的信号传导。这将如何实现？少突胶质细胞 表达许多规范后突触因子，表面上是有助于轴突和髓磷脂鞘之间的信号传导 但是这些蛋白质在髓鞘细胞中的作用在很大程度上是未知的。使用斑马鱼模型，该建议 是否会利用遗传方法和体内成像来解决两个基本概念：是否存在模式 这些突触后因子在少突胶质细胞中的表达和/或定位，并做到这一点 包裹轴突身份；它们在髓鞘中发挥了什么作用。这将被实现 在两个目标中：AIM 1测试表达了哪些突触后因素，这些突触后蛋白本地化， 它们什么时候重要； AIM 2测试这些蛋白质如何促进髓鞘，以及是否在那里 是轴突身份与骨髓中突触后蛋白的定位和功能之间的相关性 少突胶质细胞。